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The Washington Research Foundation Fellowship
Cynthia Hsu, Biochemistry; Molecular, Cellular, Developmental Biology - 2009-10 WRF/Space Grant
As a little girl, every morning, I would run down the stairs and skip into the “hospital-smelling” hallway that connected to my father’s clinic in a rural village in Taiwan, and proceed to be underfoot with my curiosity. From an early age, I have always been interested in understanding the intricacies of cellular mechanisms that cause disease. Beginning research with Dr. Merrill Hille in my freshman year at the UW has only increased my excitement for designing and conducting new experiments and elucidating biochemical pathways that induce biological functions. I am now applying for MD/PhD programs in hopes of being able to provide both immediate medical attention and the possibility of new treatments for my patients. I hope that my research training will assist me in performing human genetics translational research, particularly identifying genetic malformations and how they confer a mechanism for disease at the molecular level. I am especially interested in early onset forms of psychological/neurological diseases such as epilepsy, autism, and schizophrenia. Ultimately, I also hope to take part in introducing novel genetic therapies to my patients.
Mentor: Merrill Hille, Biology
Project Title: The Effect of p120 Catenin and its Signaling Pathway on Cell Motility in Zebrafish Gastrulation
Abstract: Gastrulation is a crucial step in embryogenesis, creating differentiation between ectoderm, mesoderm, and endoderm and forming necessary organs. On the molecular level, transmembrane and juxtamembrane proteins located at the adherens junction, such as cadherins and p120 catenin respectively, work together to either promote cell motility or adhesion, which we study using the zebrafish embryo model. We hypothesized that when p120 catenin is at the plasma membrane, it binds and stabilizes the cadherins, causing cell clustering and increased adhesion, and when p120 catenin is in the cytoplasm, it activates Rad and inhibits RhoA (two RhoGTPases), which causes cell motility. By morpholino induced knockdown, we found that p120 catenin depletion caused defects consistent with the loss of cellular migration. In addition, increasing levels of Rad mRNA in embryos create abnormal embryos, but Rad mRNA in moderation has the ability to rescue p120 catenin-depleted embryos. These results demonstrate that p120 catenin is crucial for normal cell motility in developing zebrafish embryos and suggest that a balance of p120 catenin and Rad is also necessary for normal embryogenesis. These studies on the regulation of cell motility can help to elucidate larger signaling pathways, leading to additional effects on cell survival, growth, and invasiveness, all of which may be caused by the upstream p120 catenin.